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Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway

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Abstract

Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine treatment inhibited the growth of Eca-109, TE-1 and TE-10 cells in a concentration-dependent manner as measured by MTT assay. Morphological observation, DNA laddering detection and flow cytometry analysis demonstrated that swainsonine treatment induced Eca-109 cell apoptosis in vitro. Further results showed that swainsonine treatment up-regulated Bax, down-regulated Bcl-2 expression, triggered Bax translocation to mitochondria, destructed mitochondria integrity and activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c, which in turn activated caspase-9 and caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis. Moreover, swainsonine treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activation in xenograft tumour cells, resulting in a significant decrease of tumour volume and tumour weight in the swainsonine-treated xenograft mice groups compared with that in the control group. Taken together, this study demonstrated that swainsonine inhibited Eca-109 cells growth through activation of mitochondria-mediated caspase-dependent pathway.

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Abbreviations

AIF:

apoptosis inducing factor

Apaf-1:

apoptotic protease activating factor 1

COX4:

cytochrome c oxidase IV

Δψ m :

mitochondrial membrane potential

MTT:

3-(4,5-Dimetylthiazol-2-yl)-2,5 diphenyltetrazolium bromide

Smac:

second mitochondrial activator of caspases

PARP:

poly(ADP-ribose) polymerase

PVDF:

polyvinylidene difluouride

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 31072108), the Doctoral Program of Higher Education of China (Grant No. 20090204110016, 20110204110014) and the Fundamental Research Funds for the Central Universities (QN2011064). We are grateful to Yong Zhao and Kai Lei for their kind help in the animal experiments. The authors also thank Xin He for flow cytometry assay, and Li Cao for help in statistical analysis.

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Authors and Affiliations

  1. College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, P.R. China

    Zhaocai Li, Yong Huang, Feng Dong, Wei Li, Li Ding, Gaoshui Yu, Dan Xu, Yuanyuan Yang, Xingang Xu & Dewen Tong

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  1. Zhaocai Li
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  2. Yong Huang
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  3. Feng Dong
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  4. Wei Li
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  5. Li Ding
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  6. Gaoshui Yu
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  7. Dan Xu
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  8. Yuanyuan Yang
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  9. Xingang Xu
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  10. Dewen Tong
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Corresponding author

Correspondence to Dewen Tong.

Additional information

Corresponding editor: Sorab N Dalal

MS received 18 April 2012; accepted 22 August 2012

Corresponding editor: Sorab N Dalal

[Li Z, Huang Y , Dong F, Li W, Ding L, Yu G, Xu D, Yang Y, Xu X and Tong D 2012 Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway. J. Biosci. 37 1–12] DOI 10.1007/s12038-012-9265-8

Zhaocai Li and Yong Huang contributed equally to this work.

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Li, Z., Huang, Y., Dong, F. et al. Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway. J Biosci 37 (Suppl 1), 1005–1016 (2012). https://doi.org/10.1007/s12038-012-9265-8

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  • DOI: https://doi.org/10.1007/s12038-012-9265-8

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